Japanese encephalitis virus (JEV) is the prototype virus of the Japanese encephalitis (JE) group belonging to the Flavivirus genus of the Flaviviridae family. Other members of the group include Kunjin virus, St. Louis encephalitis virus (SLEV) and West Nile encephalitis virus (WNV). JEV is widely distributed in South Asia, Southeast Asia, and the Asian Pacific Rim. In recent years, JE epidemics have spread to previously unaffected areas, such as northern Australia (Hanna, et al. (1996) Med J Aust 165:256-60; Pyke, et al. (2001) Am J Trop Med Hyg 65:747-53), Pakistan (Igarashi, et al. (1994) Microbiol Immunol 38:827-30), India and Indonesia (Mackenzie, et al. (2004) Nat Med 10:S98-109). The JE outbreak in India during July-November of 2005 was the longest and most severe in recent years, affecting in excess of 5,000 persons and causing greater than 1,000 deaths (Parida, et al. (2006) Emerg Infect Dis 12:1427-30).
It is estimated that JEV causes 35,000-50,000 cases of encephalitis, including 10,000 deaths and as many neurologic sequelae each year (Tsai (2000) Vaccine 18 Suppl 2:1-25). Although only one JEV serotype is known to exist, cross-neutralization experiments have demonstrated antigenic differences among JEV strains (Ali & Igarashi (1997) Microbiol Immunol 41:241-52). Phylogenic studies have identified five JEV genotypes, four of which are presently recognized (Chen, et al. (1992) Am J Trop Med Hyg 47:61-9; Solomon, et al. (2003) J Virol 77:3091-8; Uchil & Satchidanandam (2001) Am J Trop Med Hyg 65:242-51). The wide geographical distribution and the existence of multiple strains, coupled with the high rate of mortality and residual neurological complications in survivors, make JEV infection an important public health problem.
The JE-VAX® vaccine currently available in most countries is an inactivated whole virus vaccine prepared from virus grown in mouse brain and a three-dose regimen is required for young children (Monath (2002) Curr Top Microbiol Immunol 267:105-38). The requirements of multiple doses and the high vaccine manufacturing cost have prevented many countries from adopting an effective JEV vaccination campaign. A live attenuated vaccine, JEV strain SA14-14-2, has been developed in China and was efficacious after one dose in a recent case-controlled study (Tandan, et al. (2007) Vaccine 25:5041-5). In addition, there is a chimeric JEV vaccine constructed from the attenuated yellow fever 17D strain in a late experimental stage (Monath, et al. (2003) J Infect Dis 188:1213-30). However, until a JEV vaccine becomes generally available, a need remains for short-term prevention and therapeutic intervention of encephalitic JEV infections.